Regenerative therapies with genes and cellular agents are being developed for restoration of function in in-farcted myocardium along with many other minimally invasive cardiac and noncardiac investigative and therapeutic interventions with steerable catheters as alternatives to risky, costly, and demanding surgery. A real-time, nonfluoroscopic, portable, and cost-effective solution for steerable catheter navigation repre- sents a common and critical need for guidance of the miniminally invasive interventions. Fluoroscopy, elec- tromechanical mapping, or magnetic resonance imaging have limited ability to fulfill these requirements, in- volve exposure to radiation, and require a specialized team and a dedicated room. We propose an approach that satisfies all these requirements and is to be tested in a specific field of in- tracardiac navigation, although its anticipated utility is broad. We capitalize on our innovative working proto- type of an Acoustically Active Catheter (AAC): A tip of a steerable catheter is outfitted with a piezoelectric crystal that vibrates at a prescribed frequency and acts as a "beacon" detectable in ultrasound scan planes. As such, the tip of the AAC can be guided along ultrasound scan planes toward a testing anatomic target. Aim 1: Characterize, optimize, and initially test operating modes of the acoustic catheter. Receive, interfer- ence, and transmission operating modes of the crystal vibrating at the AAC tip are proposed and will be ex- plored to make the tip optimally and unambiguously detectable in ultrasound navigation scan planes. Aim 2: Test the precision, accuracy, and utility of the AAC navigation system. Biplane transthoracic Doppler scan planes, generated in real-time by 4-dimensional echocardiography, will be tested as a novel concept of navigation pathways for steering the AAC tip towards a testing anatomic target within the heart. The proposed approach disrupts the current status quo by introducing an innovative acoustically active catheter and, in conjunction with 4D echo imaging and navigation, an integrated ultrasound image-guided navigation system for minimally invasive interventions. PUBLIC HEALTH RELEVANCE: Infarction-related heart failure remains a major cause of morbidity and mortality in the Western world. Deliv- ery of genes or stem cells directly into the cardiac muscle by using minimally invasive interventions can re- store its function. The minimally invasive interventions are being developed also for many other cardiac and noncardiac investigative and therapeutic applications, and are based on accessing a target organ only through a minimal skin and vascular puncture with special tools including steerable catheters. In this way, a risky, costly, and demanding surgery can be avoided. The common need of the minimally invasive interventions is navigation to an anatomic target. However, a system that does not require exposure to X-rays, expensive imaging devices, or a specialized room - and yet, accurately navigates the minimally invasive intervention tool, such as a steerable intracardiac catheter - does not exist. We propose to explore a solution that capitalizes on our innovative Acoustically Active Catheter. The distal end of such a catheter produces a unique acoustic signal that is detected in ultrasound images as a "bea- con". By depicting the heart and the specific anatomic target with ultrasound, the novel catheter can be navigated by the very same technique. Thus, the relatively inexpensive, portable, and broadly available ul- trasonography has a role as both an imaging and navigation tool. This grant application is designed to initially validate the feasibility, precision, and accuracy of the proposed ultrasound image-guided navigation system.